Expression of Rho Kinase and Its Mechanism in the Left Atrial Appendage in Patients with Atrial Fibrillation


  • Yongqing Chen Department of Cardiology, Lanzhou General Hospital, Lanzhou, China
  • Fangju Su Department of Cardiology, Lanzhou General Hospital, Lanzhou, China
  • Juanping Han Department of Cardiology, Lanzhou General Hospital, Lanzhou, China
  • Piqi Jiao Department of Cardiology, Lanzhou General Hospital, Lanzhou, China
  • Wenyun Guo Department of Cardiology, Lanzhou General Hospital, Lanzhou, China



ROCK-1, MYPT-1, Cx40, Cx43, atrial fibrillation, LAA


Aim: To study the expression of Rho kinase (Rho associated coil forming protein kinase-1, ROCK-1) and its substrate myosin phosphatase target subunit 1 (myosin phosphatase target subunit-1, MYPT-1), connexin 40 (Cx40) and connexin 43 (Cx43) in the left atrial appendage of patients with atrial fibrillation, and explore the role of ROCK signaling pathway in patients with atrial fibrillation and its underlying mechanism. 

Methods: 40 patients undergoing open heart surgery were divided into two groups; atrial fibrillation group (AF group) and sinus rhythm group (SR group). About 100 mg of left atrial appendage tissue was taken during surgery and quickly frozen in liquid nitrogen. Immunohistochemistry and western blot were performed to evaluate the expression and location of ROCK-1, MYPT-1, Cx40 and Cx43 in the left atrial appendage tissue. 

Results: The results indicated that the expression of ROCK-1, MYPT-1, and Cx40 in the left atrial appendage in patients with atrial fibrillation was significantly upregulated (P < .01), the difference in the two groups was statistically significant, and ROCK-1, Cx40, and MYPT-1 expression in the AF group were higher than those in sinus rhythm group; there was a weakly positive expression of Cx43 protein in the AF group and sinus rhythm group, the difference was not statistically significant, and ROCK-1 and MYPT-1 expression showed a significant positive correlation (r = 0.968,
P < .05), MYPT 1 and Cx40 protein expression was also positively correlated (r = 0.983, P < .05). Evidence in the left atrial appendage tissue of patients with atrial fibrillation showed that some proteins in Rho/ROCK pathway were upregulated, and MYPT-1 and Cx40 protein expression in AF group were significantly higher than that of SR group, which was also positively correlated; Cx43 showed a weak positive expression in both the SR group and AF group, which indicates that Rho kinase may induce expression of Cx40 by phosphorylation of MYPT-1; Cx43 may not be involved, suggesting that Rho kinase signaling pathway may activate and play an important role in the pathogenesis of atrial fibrillation lesions.


Chapados R, Abe K, Ihida-Stansbury K, et al. 2006. ROCK controls matrix synthesis in vascular smooth muscle cells: coupling vasoconstriction to vascular remodeling. Circ Res 99:837-44.

Dupays L, Mazurais D, Rücker-Martin C, et al. 2003. Genomic organization and alternative transcripts of the human Connexin40 gene. Gene 305:79-90.

Furuyama T, Komori K, Shimokawa H, et al. 2006. Long-term inhibition of Rho kinase suppresses intimal thickening in autologous vein grafts in rabbits. J Vasc Surg 43:1249-56.

Higashi M, Shimokawa H, Hattori T, et al. 2003. Long-term inhibition of Rho-kinase suppresses angiotensin II-induced cardiovascular hypertrophy in rats in vivo: effect on endothelial NAD(P)H oxidase system. Circ Res 93:767-75.

Ishizaki T, Naito M, Fujisawa K, et al. 1997. p160ROCK, a Rho-associated coiled-coil forming protein kinase, works downstream of Rho and induces focal adhesions. FEBS Lett 404:118-24.

Ito K, Hirooka Y, Kishi T, et al. 2004. Rho/Rho-kinase pathway in the brainstem contributes to hypertension caused by chronic nitric oxide synthase inhibition. Hypertension 43:156-62.

Jansen JA, van Veen TA, de Bakker JM, et al. 2010. Cardiac connexins and impulse propagation. J Mol Cell Cardiol 48:76-82.

Kandabashi T. 2000. Inhibition of myosin phosphatase by upregulated rho-kinase plays a key role for coronary artery spasm in a porcine model with interleukin-1beta. Circulation 101:1319-23.

Kandabashi T, Shimokawa H, Mukai Y, et al. 2002. Involvement of rho-kinase in agonists-induced contractions of arteriosclerotic human arteries. Arterioscler Thromb Vasc Biol 22:243-8.

Kimura K, Ito M, Amano M, et al. 1996. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science 273:245-8.

Loirand G, Guerin P, Pacaud P. 2006. Rho kinases in cardiovascular physiology and pathophysiology. Circ Res 98:322-34.

Mam V, Tanbe AF, Vitali SH, et al. 2010. Impaired vasoconstriction and nitric oxide-mediated relaxation in pulmonary arteries of hypoxia- and monocrotaline-induced pulmonary hypertensive rats. J Pharmacol Exp Ther 332:455-6.

Narumiya S. 1996. The small GTPase Rho: cellular functions and signal transduction. J Biochem 120:215-28.

Noma K, Oyama N, Liao JK. 2006. Physiological role of ROCKs in the cardiovascular system. Am J Physiol Cell Physiol 290:C661-8.

Nossaman BD, Nossaman VE, Murthy SN, et al. 2010. Role of the RhoA/Rho-kinase pathway in the regulation of pulmonary vasoconstrictor function. Can J Physiol Pharmacol 88:1-8.

Pellman J, Lyon RC, Sheikh F. 2010. Extracellular matrix remodeling in atrial fibrosis: mechanisms and implications in atrial fibrillation. J Mol Cell Cardiol 48:461-7.

Rackauskas M, Neverauskas V, Skeberdis VA. 2010. Diversity and properties of connexin gap junction channels. Medicina (Kaunas) 46:1-12.

Severs NJ, Coppen SR, Dupont E, et al. 2004. Gap junction alterations in human cardiac disease. Cardiovasc Res 62:368-77.

Shatanawi A, Romero MJ, Iddings JA, et al. 2011. Angiotensin II-induced vascular endothelial dysfunction through RhoA/Rho kinase/p38 mitogen-activated protein kinase/arginase pathway. Am J Physiol Cell Physiol 300: C1181-92.

Shimokawa H, Takeshita A. 2005. Rho-kinase is an important therapeutic target in cardiovascular medicine. Arterioscler Thromb Vasc Biol 25:1767-75.

Uehata M, Ishizaki T, Satoh H, et al. 1997. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389:990-4.

Wang N, Guan P, Zhang JP, et al. 2010. Fasudil hydrochloride hydrate, a Rho-kinase inhibitor, suppresses isoproterenol-induced heart failure in rats via JNK and ERK1/2 pathways. J Cell Biochem 112:1920-9.

Wettschureck N, Offermanns S. 2002. Rho/Rho-kinase mediated signaling in physiology and pathophysiology. J Mol Med (Berl) 80:629-38.

Zhou Q, Gensch C, Liao JK. 2011. Rho-associated coiled-coil-forming kinases (ROCKs): potential targets for the treatment of atherosclerosis and vascular disease. Trends Pharmacol Sci 32:167-73.



How to Cite

Chen, Y., Su, F., Han, J., Jiao, P., & Guo, W. (2018). Expression of Rho Kinase and Its Mechanism in the Left Atrial Appendage in Patients with Atrial Fibrillation. The Heart Surgery Forum, 21(1), E044-E048.




Most read articles by the same author(s)